The objectives of this project are to design and utilize neutral acyclic ionophores. We have begun with a dioxasuberic diamide system which selectively complexes Calcium (recently described by Simon et al). In collaboration with Professor W. Simon (Swiss Federal Institute of Technology, Zurich), we hope to define the optimum features of this system for the selective chelation of several divalent and monovalent cations of biological interest; especially Calcium, and also magnesium, barium and potassium. By suitable change of the oxygen coordinating sites of this system to "softer" nitrogen and/or sulfur sites, we hope to also develop selective chelatin for large "soft" cations such as Hg ion 2, Pb ion 2 and Cu ion 2. Other modifications will attempt to change the coordination number from 6 to 8 and possibly larger values. Our basic system is capable of great synthetic variation including the introduction of fluorescent, aromatic, and alicyclic moieties. It is not limited to cyclic structures with fixed "cavities" which are found in some presently available systems. The synthesis of most of our systems appears to be straightforward. The compounds prepared will be tested by us for ion complexation by several methods including potentiometry (with an ion-selective electrode meter), spectral changes, conductivity changes, solubilization and the isolation of crystalline complexes for X-ray analysis. The more promising compounds will be tested as substrates in ion-selective electrodes by Prof. Simon and for ion-transport properties by Prof. B. Pressman (Univ. of Miami Medical College). We hope to approach the behavior of antibiotic X-537A in the regulation of calcium transport and the initiation of heart muscle contraction.